Liver is a viscus having a powerful ability of regeneration in a body. The mechanism of regulation of liver has been searched for more than 100 years. However, the action of the growth factors associated with liver regeneration as known presently, e.g. hepatocyte growth factors (HGF), transforming growth factor-α (TGF-α), and the like, lacks the specificity for liver, and thus it is difficult to explain the organ-specific regulation mechanism of liver regeneration. Therefore, the studies in this field have been focused on the search of novel regulation factors of liver regeneration. In the 1950s, it was discovered that, in mammalian liver, there are some substances capable of regulating its growth[1]. In 1975, LaBrecque et al.[2] for the first time reported that there is a thermostable mixture, which can specifically promote hepatocyte proliferation, in the regenerated liver tissue of rat, and this mixture is referred to as hepatic stimulator substance (HSS). In the mid-1980s, the same kind of factors were discovered in human fetal liver tissue by the inventors, and the corresponding bioactivity, physicochemical properties, purification of proteins and clinical application were systemically studied. Since this kind of factors exhibited an excellent therapeutic effect in the clinical treatment of sever liver injury, and thus they were of great interest and a relevant US patent was obtained in 1995[3]. However, the components therein were not further identified due to the limitation of the techniques for purifying and identifying proteins, which limits the further development and application of such substances. Meanwhile, the molecular cloning of this kind of factors has been studied in many laboratories worldwide. In 1995, Hagiya et al.[4] isolated an augmenter of liver regeneration from the regenerated liver tissue of rat and performed the cloning and expression thereof, and it was discovered that the recombinant augmenter of liver regeneration could promote the liver regeneration of the partially hepatectomized rat, but did not have the activity of stimulating the primary-cultured hepatocytes and the liver cell lines in vitro[5].
In recent years, the inventors isolated a new hepatocyte growth factor from the liver of newborn calf by utilizing several isolation processes, and it has been discovered that this hepatocyte growth factor can promote the DNA synthesis of hepatocyte and has a protective effect against the acute or chronic liver injury. This hepatocyte growth factor is designated as HPPCn. The sequence analysis thereof showed that it belongs to the family of leucine-rich acidic nuclear protein (LANP). LANP is a multifunctional acidic nuclear protein, which is involved in a variety of biological processes including signal transduction, protein degradation, cytoskeletal dynamics, and morphogenesis[6-13]. However, it is not reported that LANP as a growth factor can stimulate hepatocyte proliferation or liver regeneration.
There are more than 120 millions of patients suffering from viral hepatitis, cirrhosis and/or liver cancer in China Therefore, developing an active factor capable of specifically promoting hepatocyte proliferation and liver regeneration, is of significance for the treatment of liver injury due to various causes.
In addition, the malignant tumors, such as liver cancer, and the like, become one of main killers for human health, and thus it is very socially important to inhibit the growth of tumor cells or tumorigenesis.